Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Flow cytometric assessment of leukemia-associated monocytes in childhood B-cell acute lymphoblastic leukemia outcome.

Abstract

Relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) remains a leading cause of cancerrelated death in children.1,2 Despite an extensive understanding of leukemia-intrinsic drivers of disease relapse,3 the role of the leukemia microenvironment in promoting leukemic blast survival remains unclear.4 To address this, we and others have shown B-ALL blasts significantly remodel the immune microenvironment composition, particularly increasing representation of nonclassical monocytes (ncMono; CD14–CD16+) within the leukemia-associated myeloid compartment.5-7 Previous studies suggest classical monocytes give rise to ncMonos8,9 that can then act, in part, to maintain vascular endothelial integrity,10 however, the specific function of ncMonos in B-ALL pathogenesis remains unclear. Furthermore, we demonstrated that high monocyte abundance in peripheral blood (PB) at initial diagnosis was associated with an inferior outcome in both adults and children with B-ALL. These initial studies used single cell RNA-sequencing analysis on a small cohort of patients with diagnosis, remission, and relapse B-ALL biospecimens; however, we did not analyze individuals who achieved prolonged disease remission and relied on total monocyte abundance as a surrogate marker of ncMono. To validate the association of ncMono in a much larger cohort of B-ALL diagnosis samples, we examined the relationship between bone marrow (BM) and PB ncMono, and to specifically study the prognostic impact of ncMono, we performed high-parameter flow cytometry on primary matched B-ALL diagnosis BM and PB from children enrolled in the Children’s Oncology Group (COG) protocols.